Competitive substrate inhibition in the histochemistry of cholinesterase activity in Alzheimer's disease.
We used acetylcholine and butyrylcholine to competitively inhibit the cleavage of acetylthiocholine or butyrylthiocholine in plaques and tangles of Alzheimer's disease. Butyrylcholine was much more effective than acetylcholine in reducing the histochemical reaction for acetylcholinesterase not only in neuronal fibers, but also in plaques and tangles. This is in keeping with biochemical data on acetylcholinesterase and supports the existence of true acetylcholinesterase activity within plaques and tangles. However, 2-4 times higher acetylcholine and buturylcholine concentrations were necessary to inhibit the plaque and tangle bound enzyme. Together with the previously reported different pH optima, this suggests that the plaque- and tangle-bound acetylcholinesterase may represent an altered form of this enzyme.
Schätz
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Bullard and Denny-Brown Laboratories, Division of Neuroscience and Behavioral Neurology, Beth Israel Hospital, Harvard Medical School, Boston, MA.
Geula
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Mesulam
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D000110:Acetylcholinesterase / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D001667:Binding, Competitive; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D002091:Butyrylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000378:metabolism*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D012016:Reference Values
D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase